Contrast enhancement in optical coherence tomography

Molecular imaging is a powerful tool for studying disease progression and potential therapies in animals. Optical coherence tomography (OCT) is an important biomedical imaging modality, filling the niche between ultrasound and microscopy. However, OCT suffers from an inherent lack of molecular contrast (the ability to distinguish a molecule of interest from others). This is because the scattering cross-section, the source of contrast in this technique, does not vary widely between molecular species. Researchers have worked around this problem by using OCTwith either endogenous or exogenous sources of contrast in a number of schemes.1, 2 But these methods require computermodeling to decouple scattering from absorption, and they depend on the elastic properties of the tissue. An alternative technique relies on specialized opticalabsorption contrast agents that enhance the visibility of the molecule of interest by emitting detectable heat when they absorb infrared light. We and others demonstrated that this photothermal detection of contrast agents can be achieved by incorporating an amplitude-modulated laser into the sample arm of a standard OCT system.3–7 This approach has the advantage of allowing for noninvasive in vivo molecular imaging in three dimensions. In photothermal imaging, strong optical absorption by a target of interest—such as a nanoparticle—results in a change in temperature around the particle (i.e., the photothermal effect). Local photothermal heating causes index-of-refraction changes and thermoelastic expansion in the microenvironment surrounding the absorber, thus altering the local optical path length. Changes in the optical path length due to photothermal heating can be imaged directly via the phase information in an OCT image because of the linear relationship between the two parameters. This method, called photothermal OCT (PTOCT), is advantageous because it allows for sensitive detection of absorbing contrast agents over a scattering tissue background without the use of modeling and with minimal effects from tissue properties. Figure 1. Photothermal optical coherence tomography (PTOCT) instrumentation schematic. A fiber-coupled OCT system sends light from the broadband super-luminescent diode (SLD) source to the sample and reference arms (split by the 50/50 fiber splitter), and the returning light is detected by the spectrometer and CCD at 10kHz. The photothermal laser is amplitude-modulated (to create photothermal oscillations in the sample) and fiber coupled into the sample arm. Adapted with permission from the Optical Society of America.7